Triethylamine → 4-(Trimethylsilylethynyl)benzaldehyde

HRID 2253287Notes

Reaction equation

HRID 2253287 reaction equation
Br[C:2]1[CH:9]=[CH:8][C:5]([CH:6]=[O:7])=[CH:4][CH:3]=1.C(N(CC)CC)C.[C:17]([Si:19]([CH3:22])([CH3:21])[CH3:20])#[CH:18]>C1COCC1.[Cu]I>[CH3:20][Si:19]([C:17]#[C:18][C:2]1[CH:9]=[CH:8][C:5]([CH:6]=[O:7])=[CH:4][CH:3]=1)([CH3:22])[CH3:21]

Participants

6

Reactant 3

HCID 8471TriethylamineHCID 66111TrimethylsilylacetyleneHCID 707414-Bromobenzaldehyde

Product 1

HCID 27716434-(Trimethylsilylethynyl)benzaldehydeYield 67.7%

Reagents, catalysts & solvents 2

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
30 °C

Procedure

4-Bromobenzaldehyde (1) (185 g, 1.0 mole) was dissolved in THF (1 L) followed by addition of copper (I) iodide (7.6 g, 0.04 mol), dicholobis(triphenylphospine) palladium (II) (14.02 g, 0.02 mol) and triethylamine (151.5 g, 1.5 mol). Ethynyltrimethylsilane (109.1 g, 1.11 mol) was added from addition funnel as a solution in THF (0.2 L). The reaction was stirred at 30° C. for 30 min and then at 25° C. for 20 hours. Analysis by HPLC indicated the completion of the reaction. THF was removed and the residue was treated with hexane (1.8 L). The solid was removed by filtration and the filter cake washed with hexane (0.3 L). The combined hexane solution was washed with water (2×0.5 L). Hexane was removed in a rotovap. The residue was dissolved in EtOH (0.5 L) at 50° C. The solution was then slowly cooled to 16° C. and was stirred for 30 minutes. Product started to crystallize. The mixture was further cooled to 5° C. 1:1 of EtOH/H2O (0.24 L) was added slowly. The mixture was stirred at 5° C. for 30 minutes. Solid was collected by filtration, washed with 4:1 of EtOH/H2O (0.2 L) and dried to provide 137.0 g of product. The mother liquor was concentrated to dryness. The residue was partitioned between hexane (0.5 L) and brine (0.25 L). Hexane layer was separated and concentrated to dryness. The residue was crystallized from hexane (40 ml) and further recrystallized from 4:1 of EtOH/H2O (0.1 L) to provide second crop of aldehyde 2 (27.0 g). The combined yield for aldehyde 2 was 81%. 1H NMR (300 MHz, CDCl3) δ 0.081 (s, 9H), 7.41 (d, 2H, J=8.1 Hz), 7.63 (d, 2H, J=8.4 Hz), 9.81 (s, 1H).

Workup

  1. waitat 25° C. for 20 hours
  2. customthe completion of the reaction
  3. customTHF was removed
  4. additionthe residue was treated with hexane (1.8 L)
  5. customThe solid was removed by filtration
  6. washthe filter cake washed with hexane (0.3 L)
  7. washThe combined hexane solution was washed with water (2×0.5 L)
  8. customHexane was removed in a rotovap
  9. dissolutionThe residue was dissolved in EtOH (0.5 L) at 50° C
  10. temperatureThe solution was then slowly cooled to 16° C.
  11. stirringwas stirred for 30 minutes
  12. customto crystallize
  13. temperatureThe mixture was further cooled to 5° C
  14. addition1:1 of EtOH/H2O (0.24 L) was added slowly
  15. stirringThe mixture was stirred at 5° C. for 30 minutes
  16. filtrationSolid was collected by filtration
  17. washwashed with 4:1 of EtOH/H2O (0.2 L)
  18. customdried

Sources & evidence

ORD record
ord-007bc8d526584002a1b7450d069cc6d9
Source dataset
uspto-grants-2008_01
Patent number
US07323562B2

Reaction notes

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